The present invention comprises the surprising and unexpected discovery that administration of a cytoprotective prostaglandin provides a useful method for treatment of certain diseases of the human small or large intestine.
Certain pharmacological uses of prostaglandins or prostaglandin analogs in the treatment or prophylaxis of gastrointestinal tract disorders are known in the art. For example, the use of prostaglandin-type compounds effective in reducing gastric secretion and in the cure of prophylaxis of gastric or duodenal ulcers is known. See U.S. Pat. Nos. 3,903,297 and 3,781,429. Further, the concomitant use of prostaglandin-type compounds with a NOSAC (nonsteroidal antiinflammatory compound which is a prostaglandin synthetase inhibitor) is known to be effective to reduce known undesirable gastrointestinal side effects of NOSAC administration. See U.S. Pat. Nos. 3,911,124; 3,917,828; 3,928,588; and 3,927,213.
Finally, the use of PGE.sub.2 to prevent damage to the gastric mucosal barrier in the dog when the gastric mucosal barrier is subjected to attack by aspirin or indomethacin is described in Gastroenterology 68:A-19/876 (April, 1975).
As used herein, the term prostaglandin refers to those cyclopentane-containing carboxylic acids derived from mammalian tissues which are structural derivatives of prostanoic acid: ##STR1## See Bergstrom, et al. Pharmacol. Rev. 20, 1 (1968) and references cited therein. For example, prostaglandin E.sub.2 (PGE.sub.2) exhibits the following structure: ##STR2##
The term prostaglandin analog herein refers to those compounds structurally related to the prostaglandins (in that they exhibit a cyclopentane, or adjacently homologous cycloalkane, ring and a pair of side chains attached to adjacent carbon atoms of the ring) which retain characteristic biological properties of the prostaglandins. See Bergstrom, cited above. Various structural modifications of the prostaglandins are known to produce useful prostaglandin analogs. For example, the replacement of the carboxy with a hydroxymethyl is known, substitution of a methyl, ethyl, or fluoro for a hydrogen at, for example, C-2 or C-16, and replacement of a methylene by an oxa or thia at, for example, C-5 is known. Further, partially deoxygenated prostaglandins are known to be useful prostaglandin analogs. Accordingly, 9-deoxy, 11-deoxy, and 15-deoxy-prostaglandins are known. Finally, there are known prostaglandin analogs wherein the double bonds of, for example, PGF.sub.2.alpha. are shifted, e.g., cis-4,5-didehydro-PGF.sub.1.alpha., or replaced by triple bonds, e.g., 13,14-didehydro-PGF.sub.2.alpha..
As used herein, the term prostaglandin-type compound refers to any prostaglandin or prostaglandin-analog.